Nature Medicine
2, 461 - 462 (1996)
doi:10.1038/nm0496−461
Matrix metalloproteinase−1 is associated with poor prognosis in colorectal cancerGraeme I. Murray1, 3, Margaret E. Duncan2, Pauline O'Neil1, William T. Melvin2
& John E. Fothergill2
1Department of Pathology, University of Aberdeen, Aberdeen, AB9 2ZD, UK
2Department of Molecular & Cell Biology, University of Aberdeen, Aberdeen, AB9 2ZD, UK
3Correspondence should be addressed to G.I.M. Colorectal cancer is one of the commonest malignant tumors and has a relatively poor prognosis. The outcome depends on the extent of local and particularly metastatic tumor spread. The matrix metalloproteinases (MMPs) are a family of closely related enzymes that degrade the extracellular matrix and are considered to be important in facilitating tumor invasion and spread1−3. Using immunohistochemistry we have investigated the occurrence in colorectal cancer of MMP−1 (interstitial collagenase). Our monoclonal antibody was prepared against a synthetic peptide corresponding to an amino acid sequence specific for MMP−1 and was selected to react in formalin−fixed wax−embedded sections, thus allowing use in diagnostic histopathology and also enabling access to archival material. We found that the presence of MMP−1 in colorectal cancer is associated with a poor prognosis (P = 0.006) and has prognostic value independent of Dukes stage. One MMP inhibitor that strongly inhibits MMP−1 has already been shown to inhibit growth of human colon cancer xenografts in nude mice4. Our results suggest that treatment of those individuals whose colon tumors produce MMP−1 with MMP inhibitors is a therapeutic strategy worth pursuing.
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